DESCRIPTION: This study will use DNA, previously collected by the applicants from a well characterized population of lung cancer cases and controls, to study two classes of genes involved in the genesis of lung cancer, including oncogenes (K-ras) and tumor suppressor genes (P53 and genes on chromosome 3p). The application proposes to study mutations at these three loci, hypothesizing that specific alterations in these genes and loss of heterozygosity at chromosome 3p will describe aetiologic subclassifications associated with epidemiologically defined patterns of exposure to carcinogens of interest (e.g., smoking and asbestos) modified by the polymorphic metabolic traits and diet. Fundamental to this application is the hypothesis that lung cancers arise through different pathways and that these pathways reflect the patterns of exposure and susceptibility of individuals to the action of aetiologically important patterns of exposure and susceptibility of individuals to the action of aetiologically important carcinogens. The relationship of alterations in these genes to DNA adduct burden in normal lung tissue will be examined, along with mononuclear cell DNA.